Bicaudal D2 autoantibodies are highly specific for systemic sclerosis.

OBJECTIVE: Autoantibodies directed against the intracellular protein bicaudal D2 (BICD2) have been identified as a specific marker of systemic sclerosis (SSc). Since autoantibodies are of value in predicting disease onset and identifying meaningful clinical subsets, as well as having prognostic value, this study aimed to establish the prevalence of BICD2 autoantibodies (anti-BICD2) in a cohort of patients with connective tissue disease and healthy controls. METHOD: In this cross-sectional study, 363 patients with connective tissue disease (121 SSc, 141 systemic lupus erythematosus, 101 myositis, and 100 blood donors) were tested for the presence of anti-BICD2. All SSc patients were tested for specific anti-nuclear antibodies (ANAs), and clinical and laboratory associations were evaluated in the SSc patients, stratified by anti-BICD2 status. RESULTS: In the SSc cohort, 35 patients had autoantibodies directed against BICD2. The specificity of anti-BICD2 in SSc patients was 96.5%; however, the sensitivity was only 28.9%. Anti-BICD2 and centromere autoantibodies were present together in 91% of the anti-BICD2-positive SSc patients, and in none of the cases was anti-BICD2 the only antibody present. Anti-BICD2-positive patients had lower forced expiratory volume in 1 s (FEV1) (p = 0.01) and lower carbon monoxide transfer coefficient (KCO) (p = 0.01) than anti-BICD2-negative SSc patients, but they had higher forced vital capacity (p = 0.03). CONCLUSION: Autoantibodies against BICD2 were highly specific for SSc patients. Reduced FEV1 and KCO in anti-BICD2-positive patients may indicate that the presence of anti-BICD2 is associated with altered lung function in an unknown pathophysiological manner, which awaits further elucidation.

Monocyte secretory profiling in a clinical and MEFV genotype-characterized cohort of Danish familial Mediterranean fever patients: diagnostic potential of CCL1 and CXCL1.

OBJECTIVE: The autoinflammatory disease familial Mediterranean fever (FMF), characterized by recurrent attacks of sterile fever, serosal, and/or synovial inflammation, is caused by variants in the Mediterranean fever gene, MEFV, coding for the pyrin inflammasome sensor. The diagnosis of FMF is mainly based on clinical symptoms and confirmed by detection of disease-associated MEFV variants. However, the diagnosis is challenging among patients carrying variants of uncertain clinical significance (VUS). In this study, we aimed to identify potential FMF discriminatory diagnostic markers in a cohort of clinically characterized FMF patients. METHOD: We established a cohort of clinically and MEFV genotype-characterized FMF patients by enrolling patients from major Danish hospitals (n = 91). The secretory profile of pyrin inflammasome-activated monocytes from healthy donors (HDs) and MEFV-characterized FMF patients (n = 28) was assessed by analysing cell supernatants for a custom-designed panel of 23 cytokines, chemokines, and soluble tumour necrosis factor receptors associated with monocyte and macrophage function. RESULTS: MEFV genotypes in Danish FMF patients were associated with age at symptom onset (p < 0.05), FMF among relatives (p < 0.01), proportion of patients in colchicine treatment (p < 0.01), and treatment response (p < 0.05). Secretion of chemokines CCL1 and CXCL1 from pyrin-activated FMF monocytes was significantly decreased compared to HDs (p < 0.05), and could discriminate FMF patients with 'non-confirmatory' MEFV genotypes from HDs with 80.0% and 70.0% sensitivity for CCL1 and CXCL1, respectively (p < 0.05). CONCLUSION: Our data suggest that a functional diagnostic assay based on CCL1 or CXCL1 levels in pyrin-activated patient monocytes may contribute to FMF diagnosis in patients with VUS.

Botulinum toxin treatment improves dysphagia in patients with oculopharyngeal muscular dystrophy and sporadic inclusion body myositis.

OBJECTIVE: Dysphagia can be troublesome in sporadic inclusion body myositis (sIBM) and oculopharyngeal muscular dystrophy (OPMD), but no established treatment exists. Cricopharyngeal muscle botulinum toxin injection has at case level been reported to be effective. We evaluated safety and efficacy of botulinum toxin injections in the cricopharyngeal muscle in patients with dysphagia due to sIBM or OPMD. METHODS: Participants were included from our outpatient clinic. Cricopharyngeal constriction was confirmed by laryngoscopy. After EMG confirmation of needle placement in the cricopharyngeal muscle, botulinum toxin A was injected in awake patients. An individualized dose of 5-10 units of botulinum toxin A was applied initially and titrated up a maximum of 3 times. Outcome measures were change in dysphagia questionnaire, timed cold-water swallow test and subjective dysphagia status (worse, unchanged, improved). Due to the need for individualized dosing and a limited number of available patients, an uncontrolled, un-blinded design was used. RESULTS: Thirteen patients, 3 with OPMD, received at least 1 injection. In the dysphagia questionnaire, all but 2 subjects, none with subjective worsening, improved (p < 0.001). Subjectively, seven felt an improvement, 4 no change and 2 a worsening. No overall change was seen the timed cold-water swallow test. No serious adverse events were observed. CONCLUSION: Botulinum toxin injection of the cricopharyngeal muscle in patients with OPMD and sIBM had a beneficial effect on dysphagia in most of the treated patients. Two of 13 patients experienced a temporary worsening not reflected in dysphagia score. Limitations are the un-blinded and un-randomized design and subjective assessments methods. PROSPECTIVE TRIAL REGISTRATION: EudraCT-number: 2014-002210-23.

Increased long-term risk of heart failure and other adverse cardiac outcomes in dermatomyositis and polymyositis: Insights from a nationwide cohort.

BACKGROUND: Mounting evidence suggests that dermatomyositis/polymyositis (DM/PM) are associated with increased risk of atherosclerotic events and venous thromboembolism. However, data on the association between DM/PM and other cardiac outcomes, especially heart failure (HF), are scarce. OBJECTIVES: To examine the long-term risk and prognosis associated with adverse cardiac outcomes in patients with DM/PM. METHODS: Using Danish administrative registries, we included all patients ≥18 years with newly diagnosed DM/PM (1996-2018). Risks of incident outcomes were compared with non-DM/PM controls from the background population (matched 1:4 by age, sex, and comorbidity). In a secondary analysis, we compared mortality following HF diagnosis between DM/PM patients with HF and non-DM/PM patients with HF (matched 1:4 by age and sex). RESULTS: The study population included 936 DM/PM patients (median age 58.5 years, 59.0% women) and 3744 matched non-DM/PM controls. The median follow-up was 6.9 years. Absolute 10-year risks of incident outcomes for DM/PM patients vs matched controls were as follows: HF, 6.98% (CI, 5.16-9.16%) vs 4.58% (3.79-5.47%) (P = 0.002); atrial fibrillation, 10.17% (7.94-12.71%) vs 7.07% (6.09-8.15%) (P = 0.005); the composite of ICD implantation/ventricular arrhythmias/cardiac arrest, 1.99% (1.12-3.27%) vs 0.64% (0.40-0.98%) (P = 0.02); and all-cause mortality, 35.42% (31.64-39.21%) vs 16.57% (15.10-18.10%) (P < 0.0001). DM/PM with subsequent HF was associated with higher mortality compared with HF without DM/PM (adjusted hazard ratio 1.58 [CI, 1.01-2.47]). CONCLUSION: Patients with DM/PM had a higher associated risk of HF and other adverse cardiac outcomes compared with matched controls. Among patients developing HF, a history of DM/PM was associated with higher mortality.

Blood-flow restricted resistance training in patients with sporadic inclusion body myositis: a randomized controlled trial.

OBJECTIVES: To investigate the effect of 12 weeks of low-load blood-flow restricted resistance (BFR) training on self-reported and objective physical function, and maximal muscle strength in patients with sporadic inclusion body myositis (sIBM). METHOD: Twenty-two patients with sIBM were randomized into a training group (BFR group) or a non-exercising control group, according to CONsolidated Standards Of Reporting Trials (CONSORT) guidelines. The BFR group performed 12 weeks of BFR training twice per week. The primary outcome was the physical function domain of the 36-item Short Form Health Survey (pf-SF-36), which was used to measure self-reported physical function. All patients performed physical function tests (2-Minute Walk Test, Timed Up and Go, and 30-Second Chair Stand), completed the Inclusion Body Myositis Functional Rating Scale (IBMFRS), and were tested for isolated knee extensor muscle strength. RESULTS: No effects of the training intervention were observed for pf-SF-36 or the objective physical function tests. Leg muscle strength decreased in controls (-9.2%, p = 0.02), but was unaltered in the BFR group (+0.9%, p = 0.87), resulting in a between-group difference in the per-protocol analysis (p = 0.026). Between-group differences in baseline to follow-up changes emerged for IBMFRS, in favour of the BFR group (p = 0.018). CONCLUSION: Twelve weeks of BFR training did not improve self-reported or objective physical function in these sIBM patients. However, the training protocol had a preventive (retaining) effect on the disease-related decline in leg muscle strength, which may aid the long-term preservation of physical function and postpone the need for healthcare assistance.

Cardiac Abnormalities in Adult Patients With Polymyositis or Dermatomyositis as Assessed by Noninvasive Modalities.

OBJECTIVE: Cardiac events are a major cause of death in patients with idiopathic inflammatory myopathies. The study objective was in a controlled setting to describe cardiac abnormalities by noninvasive methods in a cohort of patients with polymyositis (PM) or dermatomyositis (DM) and to identify predictors for cardiac dysfunction. METHODS: In a cross-sectional study, 76 patients with PM/DM and 48 matched healthy controls (HCs) were assessed by serum levels of cardiac troponin I, electrocardiography, Holter monitoring, echocardiography with tissue Doppler imaging, and quantitative cardiac (99m) Tc-pyrophosphate ((99m) Tc-PYP) scintigraphy. RESULTS: Compared to HCs, patients with PM/DM more frequently had left ventricular diastolic dysfunction (LVDD) (12% versus 0%; P = 0.02) and longer QRS and QT intervals (P = 0.007 and P < 0.0001, respectively). In multivariate analysis, factors associated with LVDD were age (P = 0.001), disease duration (P = 0.004), presence of myositis-specific or -associated autoantibodies (P = 0.05), and high cardiac (99m) Tc-PYP uptake (P = 0.006). In multivariate analysis of the pooled data for patients and HCs, a diagnosis of PM/DM (P < 0.0001) was associated with LVDD. CONCLUSION: Patients with PM or DM had an increased prevalence of cardiac abnormalities compared to HCs. LVDD was a common occurrence in PM/DM patients and correlated to disease duration. In addition, the association of LVDD with myositis-specific or -associated autoantibodies and high cardiac (99m) Tc-PYP uptake supports the notion of underlying autoimmunity and myocardial inflammation in patients with PM/DM.

Effects of blood-flow-restricted resistance training on muscle function in a 74-year-old male with sporadic inclusion body myositis: a case report.

Sporadic inclusion body myositis (sIBM) is a systemic disease that is characterized by substantial skeletal muscle weakness and muscle inflammation, leading to impaired physical function. The objective was to investigate the effect of low-load resistance exercise with concurrent partial blood flow restriction to the working muscles (blood-flow-restricted (BFR) training) in a patient with sIBM. The training consisted of 12 weeks of lower extremity BFR training with low training loads (~25-RM). The patient was tested for mechanical muscle function and functional capacity before and after 6 and 12 weeks of training. Maximal horizontal gait speed increased by 19%, which was accompanied by 38-92% improvements in mechanical muscle function (maximal isometric strength, rate of force development and muscle power). In conclusion, BFR training was well tolerated by the patient with sIBM and led to substantial improvements in mechanical muscle function and gait speed.